Endogenous retroviruses and retroviral-like elements reside in the genomes of all eukaryotic organisms. Most vertebrates are host to a variety of exogenous retroviruses. Infection by retroviruses can lead to diseases including, leukemias and lymphomas, solid tumors, and immunosuppressive disorders. Interaction between retroviruses and host cells appear to have important biological consequences. One example is the role that retrovirally encoded reverse transcriptases could have in the generation of processed pseudogenes, which are abundant eukaryotic genetic elements important in shaping the genome. Another example is the recombination between retroviral and cellular sequences which can lead to the generation of acutely transforming the genomes of which encode cell derived oncogenes. Several aspects of retroviral replication that effect viral as well as host sequences will be studied. Of particular interest are the determinants of retroviral genomic RNA packaging, and the consequences of encapsidation into retroviral particles of non-viral RNAs. A system called retrofection has been developed in order to study the cDNA products of cellular mRNA encapsidation. This system will be further explored in order to delineate the viral products required for cellular cDNA integration as compared to the requirements for retroviral provirus integration. Co-packaging of viral and cellular RNAs into retroviral particles is proposed as an intermediate In the generation of acutely transforming retroviruses. Using genetically defined RNAs we will study the recombination of selectable markers with replication competent retroviruses in order to determine whether stretches of identical sequences are important determinants of recombination.